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Published in: Molecular Neurodegeneration 1/2010

Open Access 01-12-2010 | Research article

Endocytic pathways mediating oligomeric Aβ42 neurotoxicity

Authors: Chunjiang Yu, Evelyn Nwabuisi-Heath, Kevin Laxton, Mary Jo LaDu

Published in: Molecular Neurodegeneration | Issue 1/2010

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Abstract

Background

One pathological hallmark of Alzheimer's disease (AD) is amyloid plaques, composed primarily of amyloid-β peptide (Aβ). Over-production or diminished clearance of the 42 amino acid form of Aβ (Aβ42) in the brain leads to accumulation of soluble Aβ and plaque formation. Soluble oligomeric Aβ (oAβ) has recently emerged to be as a likely proximal cause of AD.

Results

Here we demonstrate that endocytosis is critical in mediating oAβ42-induced neurotoxicity and intraneuronal accumulation of Aβ. Inhibition of clathrin function either with a pharmacological inhibitor, knock-down of clathrin heavy chain expression, or expression of the dominant-negative mutant of clathrin-assembly protein AP180 did not block oAβ42-induced neurotoxicity or intraneuronal accumulation of Aβ. However, inhibition of dynamin and RhoA by expression of dominant negative mutants reduced neurotoxicity and intraneuronal Aβ accumulation. Pharmacologic inhibition of the dynamin-mediated endocytic pathway by genistein also reduced neurotoxicity.

Conclusions

These data suggest that dynamin-mediated and RhoA-regulated endocytosis are integral steps for oligomeric Aβ42-induced neurotoxicity and intraneuronal Aβ accumulation.
Appendix
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Metadata
Title
Endocytic pathways mediating oligomeric Aβ42 neurotoxicity
Authors
Chunjiang Yu
Evelyn Nwabuisi-Heath
Kevin Laxton
Mary Jo LaDu
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2010
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/1750-1326-5-19

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